Early developmental trajectories associated with ASD in infants with tuberous sclerosis complex

Jeste, Shafali; Wu, Joyce; Şentürk, Damla; Varcin, Kandice J.; Ko, Jordan; McCarthy, Brigid; Shimizu, Christina; Dies, Kira; Vogel‐Farley, Vanessa; Şahin, Mustafa; Nelson, Charles A.

doi:10.1212/wnl.0000000000000568

Cited by 71 publications

(105 citation statements)

References 34 publications

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“…In our prospective study of children with TSC, we found that developmental slowing in nonverbal cognition predicted ASD, highlighting the strong comorbidity of developmental delay and ASD in TSC, 14 and raising the question of whether ASD in TSC actually reflects a more global cognitive impairment rather than specific deficits in social communication.…”

Section: Resultsmentioning

confidence: 81%

“…Fifty percent of our TSC cohort met criteria for ASD, consistent with prior studies in TSC. 5,14 Results revealed that children with TSC and ASD demonstrate a profile of social communication impairment that, at the behavioral level, was virtually identical to that of children with nsASD; indeed, there were no individual markers that distinguished the 2 groups. This convergence was observed in the context of high comorbidity between ASD and cognitive impairment in both the TSC/ASD and nsASD groups.…”

Section: Resultsmentioning

confidence: 97%

“…This convergence was observed in the context of high comorbidity between ASD and cognitive impairment in both the TSC/ASD and nsASD groups. The comorbidity of ASD in TSC has been well-established in retrospective, [22][23][24] prospective, 5,14,25 and meta-analytic 6 studies. To date, most studies in TSC have focused on older age groups, treating ASD as a categorical outcome for classification, and they have relied on parent report for diagnoses, which can be limited in a child with multiple medical challenges that may obscure the parent's attention to subtle developmental manifestations.…”

Section: Resultsmentioning

confidence: 99%

“…The current study, which represents the endpoint analysis from a longitudinal investigation of autism risk factors in children with TSC, 14 had 2 primary aims: first, to determine the extent to which deficits associated with ASD in TSC overlap with those in toddlers with nsASD by examining item-level symptom profiles from a play-based diagnostic measure; and second, to examine cognitive profiles and epilepsy characteristics of toddlers with TSC and ASD. Given our findings of nonverbal cognitive slowing predicting ASD in children with TSC, we hypothesized that a distinctive autism symptom profile would emerge in TSC that would differentiate these toddlers behaviorally from those with nsASD.…”

mentioning

confidence: 99%

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Symptom profiles of autism spectrum disorder in tuberous sclerosis complex

Jeste

Varcin²,

Hellemann

et al. 2016

Neurology

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Objective: To determine the extent to which deficits associated with autism spectrum disorder (ASD) in toddlers with tuberous sclerosis complex (TSC) overlap with those in toddlers with nonsyndromic ASD (nsASD) and to examine cognitive function and epilepsy severity in toddlers with TSC and comorbid ASD. This is the endpoint analysis from a longitudinal investigation of ASD risk factors in children with TSC.Methods: Measures included the Autism Diagnostic Observation Schedule (ADOS), the Mullen Scales of Early Learning, and clinical epilepsy variables. A repeated-measures analysis of variance was performed with between-subjects factor of group (typically developing, TSC/no ASD, TSC/ASD, nsASD) and within-subjects factors of individual ADOS item scores in the social communication and repetitive behavior/restricted interest domains. Within the TSC group, comparisons of epilepsy characteristics and cognitive domains were performed using independentsamples t tests. Results:Children with TSC/ASD demonstrated a profile of social communication impairment that had complete convergence with nsASD. Measured social communication impairments included gestures, pointing, eye contact, responsive social smile, and shared enjoyment. This convergence was observed despite the high comorbidity between ASD and cognitive impairment in TSC.Conclusions: This study supports the clinical diagnosis of ASD in young children with TSC and demonstrates remarkable convergence of autism symptoms between TSC/ASD and nsASD. Our results strongly suggest the need for early intervention in toddlers with TSC, with treatment strategies targeting social communication function as well as broader developmental domains, before the onset of autism symptoms. Neurology ® 2016;87:766-772 GLOSSARY ADOS 5 Autism Diagnostic Observation Schedule; ANOVA 5 analysis of variance; ASD 5 autism spectrum disorder; BCH 5 Boston Children's Hospital; DQ 5 developmental quotient; EI 5 early intervention; EL 5 expressive language; EMM 5 estimated marginal mean; FM 5 fine motor; ID 5 intellectual disability; IRB 5 institutional review board; MSEL 5 Mullen Scales of Early Learning; nsASD 5 nonsyndromic autism spectrum disorder; RL 5 receptive language; TD 5 typically developing; TSC 5 tuberous sclerosis complex; UCLA 5 University of California, Los Angeles; VR 5 visual reception.Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder resulting from a TSC1/TSC2 mutation, leading to widespread growth of hamartomas in multiple organ systems, including the brain.1 Children with TSC are at high risk for neuropsychiatric syndromes that include developmental delay, intellectual disability (ID), mood disorders, and autism spectrum disorder (ASD), collectively referred to as TSC-associated neurocognitive deficits. 2,3 In fact, TSC is one of the most commonly occurring single-gene disorders associated with ASD. [4][5][6] Given the high rate of ASD in TSC and the fact that TSC is often diagnosed in utero or in early infancy, 7 TSC has been considered a model s...

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Section: Resultsmentioning

confidence: 81%

Section: Resultsmentioning

confidence: 97%

Section: Resultsmentioning

confidence: 99%

mentioning

confidence: 99%

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Symptom profiles of autism spectrum disorder in tuberous sclerosis complex

Jeste

Varcin²,

Hellemann

et al. 2016

Neurology

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“…A longitudinal cohort study compared differences between children with ASD with TSC to children with idiopathic ASD and found that syndromic ASD was similar to non-syndromic ASD in terms of their cognitive, behavioral, and social profiles 15 . Evaluation of the AOSI as an objective assessment tool to identify early ASD-associated behaviors in infants with TSC has been shown in a small prospective longitudinal cohort of infants 13 , but using the AOSI to predict later ASD risk in this population has not been previously reported. In 2012, we established the TSC Autism Center of Excellence Research Network (TACERN) , a large multicenter, prospective observational study to identify clinical, structural, and electrophysiological biomarkers predictive of ASD with the overall goal to establish an infrastructure for early detection of ASD and set the stage for future drug trials in patients with TSC who are at high risk for ASD.…”

Section: Introductionmentioning

confidence: 99%

Utility of the Autism Observation Scale for Infants in Early Identification of Autism in Tuberous Sclerosis Complex

Capal

Horn

Murray

et al. 2017

Pediatric Neurology

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Background Tuberous Sclerosis Complex (TSC) is a genetic disorder with high prevalence of associated autism spectrum disorder (ASD). Primary objectives were to determine early predictors of autism risk to identify children with TSC in most need of early interventions. The Autism Observation Scale for Infants (AOSI) was evaluated as a measure of ASD-associated behaviors in infants with TSC at age 12 months and its ability to predict ASD at 24 months. Methods Children ages 0 to 36 months with TSC were enrolled in the TSC Autism Center of Excellence Research Network (TACERN), a multicenter, prospective observational study to identify biomarkers of ASD. The AOSI was administered at age 12 months and the Autism Diagnostic Observation Schedule-2 (ADOS-2) and Autism Diagnostic Interview-Revised (ADI-R) at 24 months. Developmental functioning was assessed using the Mullen Scales of Early Learning. Children were classified as ASD or non-ASD according to the ADOS-2. Results Analysis included 79 children who had been administered the AOSI at 12 months and ADOS-2 and ADI-R at 24 months. The ASD group had a mean AOSI total score at 12 months significantly higher than the non-ASD group (11.8 ± 7.4 vs. 6.3 ± 4.7; p<0.001). An AOSI total score cut-off of 13 provided a specificity of 0.89 to detect ASD with the ADOS-2. AOSI total score at 12 months was similarly associated with exceeding cut-off scores on the ADI-R. Conclusions The AOSI is a useful clinical tool in determining which infants with TSC are at increased risk for developing ASD.

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Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?

Moavero

Kotulska

Lagae

et al. 2020

Ann Clin Transl Neurol

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Objective To evaluate the relationship between age at seizure onset and neurodevelopmental outcome at age 24 months in infants with TSC, as well as the effect on neurodevelopmental outcome of early versus conventional treatment of epileptic seizures with vigabatrin (80–150 mg/kg/day). Methods Infants with TSC, aged ≤4 months and without previous seizures were enrolled in a prospective study and closely followed with monthly video EEG and serial standardized neurodevelopmental testing (Bayley Scales of Infant Development and Autism Diagnostic Observation Schedule). Results Eighty infants were enrolled. At the age of 24 months testing identified risk of Autism Spectrum Disorder (ASD) in 24/80 children (30.0%), and developmental delay (DD) in 26/80 (32.5%). Children with epilepsy (51/80; 63.8%) had a higher risk of ASD (P = 0.02) and DD (P = 0.001). Overall, no child presented with moderate or severe DD at 24 months (developmental quotient < 55). In 20% of children abnormal developmental trajectories were detected before the onset of seizures. Furthermore, 21% of all children with risk of ASD at 24 months had not developed seizures at that timepoint. There was no significant difference between early and conventional treatment with respect to rate of risk of ASD (P = 0.8) or DD (P = 0.9) at 24 months. Interpretation This study confirms a relationship between epilepsy and risk of ASD/DD. However, in this combined randomized/open label study, early treatment with vigabatrin did not alter the risk of ASD or DD at age 2 years.

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Early developmental trajectories associated with ASD in infants with tuberous sclerosis complex

Cited by 71 publications

References 34 publications

Symptom profiles of autism spectrum disorder in tuberous sclerosis complex

Symptom profiles of autism spectrum disorder in tuberous sclerosis complex

Utility of the Autism Observation Scale for Infants in Early Identification of Autism in Tuberous Sclerosis Complex

Is autism driven by epilepsy in infants with Tuberous Sclerosis Complex?

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